Looking for the finest Covid-19 vaccine?

 The new phase of centralized free COVID-19 vaccination has begun from June 21st, and in a historic feat, 80,95,314 doses were provided on the first day of the new phase of COVID-19 vaccination. This is the world's largest single-day number of jabs. However, having a suitable and effective vaccine is just as crucial as having the free vaccines.

Which vaccine against Covid-19 is the most effective? For the past two and a half months, this has been the most frequently asked question about Covid-19. To be honest, finding a correct and legitimate response to this has been pretty difficult. In this episode, we'll attempt to solve this complex and challenging question. Let me request my viewers to watch this video patiently till the end. We'll use the prestigious medical journal “The Lancet" to discuss the efficacy of the several Covid-19 vaccines available in the market.

Before we go into the specifics of vaccine efficacy, let's have a quick look at the current immunisation status of the developed countries. Perhaps, that will help us to understand the issue in a better way.

To begin, let’s have a look at how the US vaccine rollout looks right now. According to the TIME, USA, around 44% of Americans have received both doses of the Two-shot Pfizer and Moderna drugs or a single injection of the one-dose Johnson&Johnson version of vaccine. Please note that the US has entered into the sixth month of its Covid-19 vaccine rollout. If you consider to add on the population those who have received only the first dose of Pfizer or Moderna – the total figure stands at just 50%.

On 29^th April, the Cable News Network (CNN) reported that the vaccine manufacturing companies changed shipment sizes as coronavirus vaccine demands declined. What does this actually mean? The statement of Freeman would perhaps clarify this. Lori Tremmel Freeman, CEO of County and City Health Officials told CNN, “Many of our health departments, especially those in rural America, are providing feedback that they either need smaller dosage vials or we will have to contend with waste.” This statement of Freeman came in the background of a CNN poll conducted by SSRS which states that at least 25% Americans say that they will not get the shot of vaccine.

Because of the widespread public opposition, state and municipal officials in the United States of America have asked vaccine makers to reduce the size of vaccination vials. As a result, Pfizer announced that it would offer lower package sizes. The shipment size was lowered from a pack containing 1,170 doses to a pack containing just 450 doses. The Executive Director of the Association of Immunization Managers, on the other hand, believes that a push should be made to change vaccination practises. Gradually, we've come across a few different forms of such push!

 

Free beer and marijuana are being offered by the US government in exchange for Covid-19 vaccine. The state's liquor and cannabis board recently stated that state-licensed cannabis businesses will be able to provide adults with "free joints" after their first or second immunisation at participating outlets. Across the United States, health authorities and a number of private organisations are implementing such efforts, which are aimed mostly at the younger generation. The viewers of this channel must decide whether or not it is justified to give out free beer and marijuana to young people in order to advertise the Covid-19 vaccine. In any case, while Indians have been queuing since midnight and fighting one other over a Covid jab, the United States of America is attempting to entice its countrymen to do the same.

 

Let's have a look at the situation of cumulative vaccine uptake in European Union (EU) and European Economic Area (EEA) countries (EEA). As of June 17th, 2021, less than 30% of adults in European countries have been fully vaccinated against Covid-19, with roughly 54% receiving only a single dose of the vaccine. There is a bold assertion that some indicators of reduced Covid-19 transmission can be found in Europe as a result of immunisation programmes across the continent. But, to what extent is this true? Let's take a look at some of the countries' immunisation data.

 

Bulgaria and Finland, for example, had completed immunisation for roughly 10% of their population as of May 30, 2021. Around 18 percent in Sweden, 20 percent in Austria, Norway, and France, and 21 to 23 percent in the Netherlands, Germany, Belgium, Portugal, Italy, and Spain. Almost all European countries are in a similar situation. Malta is the only European country with a vaccination rate of around 49 percent. Hungary is next, with roughly 47% of its vaccinations completed.

 

But what are the likely causes of Europe's immunisation program's dismal results? Viewers will notice that vaccine dose availability was never an issue. Take Finland as an example. The producers provided around 76 Covid-19 vaccination doses for every 100 people in Finland. However, only about 11 people out of every 100 in Finland have received the Covid vaccine. Take a look at the chart, which shows the immunisation status of some of Europe's most advanced countries.

 

Sl No.	Name of the country		Vaccinated	Availability
			(per 100	(per 100
	(Status up to 30 May, 2020)		population)	population)
1	Bulgaria		9.70	55.20
2	Finland		10.90	75.80
3	Sweden		18.20	79.90
4	Austria		20.70	70.00
5	Norway		20.70	76.90
Sl No.	Name of the country		Vaccinated	Availability
			(per 100	(per 100
			population)	population)
6	France		20.90	76.40
7	Netherlands		21.00	81.30
8	Germany		21.10	79.90
9	Belgium		22.90	75.90
10	Portugal		23.10	75.90
Sl No.	Name of the country		Vaccinated	Availability
			(per 100	(per 100
			population)	population)
11	Italy		23.50	75.10
12	Spain		23.60	71.90
13	Hungary		44.70	166.70

 

It is quite clear that despite substantial vaccine supply, the vaccination push in some of Europe's most sophisticated countries has yet to achieve sufficient success.

 

When we look at Australia and Japan, the scenario for vaccine proponents is much less favourable. As of June 17th, 2021, only approximately 3% of Australians had had a full vaccination, while about 21% had received only one dosage. As of June 17th, little over 6% of people in Japan had been fully vaccinated, while roughly 16% had just received one dosage.

 

The poor performance of many affluent countries when it comes to Covid-19 vaccination raises concerns about the vaccines' efficacy. Regarding the FDA approval of Covid-19 vaccinations, viewers should be aware that “Currently, no coronavirus vaccine is fully approved by the FDA. All the vaccines were given emergency use authorization only.

 

FDA approval of a drug, which requires a rigorous and structured process, means that data on the drug’s effects have been reviewed by the Centre for Drug Evaluation and Research which rules on whether the drug’s benefits outweigh its known and potential risks. The fact that none of the Covid-19 vaccines have received FDA clearance, demonstrates that the efficacy of such candidate vaccines could not overcome their potential dangers. That is likely the most important factor for individuals lack of interest in the Covid-19 vaccination in developed countries.

 

With this background in mind, now, we'll use Lancet to discuss the efficacy of Covid-19 vaccines. The study that we will discuss was published in Lancet Microbe on April 10th of this year.

 

At present, approximately 96 COVID-19 vaccines are at various stages of clinical development and we have the interim results of four vaccines which were published in scientific journals. These vaccines are – the Pfizer–BioNTech vaccine, the Moderna vaccine, the AstraZeneca– Oxford vaccine and the Gamaleya [Sputnik V] vaccine. We also have three studies through the US Food and Drug Administration (USFDA) briefing documents on the Pfizer–BioNTech, Moderna and Johnson & Johnson vaccines. Excerpts of these results have been widely communicated and debated through press releases and media, more than the scientific community and thus sometimes in misleading ways. Attention has focused on vaccine efficacy by comparing the reduction of the number of symptomatic cases. However, understanding the efficacy and effectiveness of vaccines in totality is less straightforward than it might seem.

 

Vaccine efficacy is generally reported as a relative risk reduction (RRR). What is relative risk reduction? Relative risk reduction is how much risk is reduced in an experimental group compared to a control group. For example, we have two groups of people. One group has been vaccinated (which is termed as experimental group) and the other group has not been vaccinated (and, is termed as control group). Let’s say, in the control group, those who were not vaccinated, 20% people died of Covid-19 and in the experimental group 5% people died of Covid-19. 20% is called as control group event rate (CER) and 5% is called as experimental group event rate (EER).

 

The formula to derive the relative risk reduction is:

RRR = (CER-EER)/CER

            = (0.20-0.05)/0.05

            = (0.15)/0.05

            = 0.3

            = 30%

In other words, the death rate in the vaccinated group is 30% less. Although relative risk reduction provides some information about risk, but it does not say anything about the actual odds of what is happening. RRR considers only participants which varies between populations and over time. Therefore, when you see a headline in the media like relative risk reductions of 95% for the Pfizer–BioNTech, 94% for the Moderna, 90% for the Sputnik V, 67% for the Johnson &Johnson, and 67% for the AstraZeneca–Oxford vaccines, the report is usually referring to relative risk which is half-truth. This leaves us with the unanswered question as to whether a vaccine with a given efficacy in the study population will have the same efficacy in another population with different levels of background risk of COVID-19. But this is an important question because transmission intensity varies between countries, affected by factors such as public health interventions and virus variants.

 

To derive an estimate of vaccine effectiveness, the absolute risk reduction (ARR) has to be calculated. Absolute risk reduction which is also called as risk difference is the absolute difference between the control group and the experimental group. While the relative risk reduction considers only the participants of the trial who could benefit from the vaccine, the absolute risk reduction (ARR), considers the whole population in terms of the difference between attack rates with and without a vaccine. Subtracting the Experimental Event Rate from the Control Event Rate yields the absolute risk reduction. If we take the previous example of relative risk reduction, the absolute risk reduction will be:

CER-EER = 0.20 – 0.05 = 0.15 = 15%

 

When computing the absolute risk reduction, the relative risk reduction of 30% was reduced to only 15%.

 

According to the Lancet Microbe study, absolute risk reductions are often overlooked, because they have a significantly smaller effect size than relative risk reductions. To understand this, let’s have a look at this chart:

 

Name of the Vaccine	Relative Risk Reduction              (RRR)	Absolute Risk Reduction              (ARR)
AstraZeneca–Oxford	67%	1.3%
Moderna	94%	1.2%
Johnson & Johnson	67%	1.2%
Gamaleya (Sputnik V)	90%	0.93%
Pfizer–BioNTech	95%	0.84%

 

With the use of only Relative Risk Reductions, and omitting Absolute Risk Reductions, the reporting bias has been introduced by the vaccine manufacturers, which affected the interpretation of vaccine efficacy. When communicating about vaccine efficacy, a full picture of what the data actually show is important. Comparisons should be based on the combined evidence that puts vaccine trial results in context and not just looking at one summary measure. Ranking the vaccines by their reported efficacies based only on the relative risk reductions is unfair. These studies that measured the efficacy and effectiveness of vaccines are based on the prevention of mild to moderate COVID-19 infection; they were not designed to conclude on prevention of hospitalisation, severe disease, or death, or on prevention of infection and transmission potential. Assessing the suitability of vaccines must consider all indicators, involving safety, deployability, availability, and costs.

 

Unfortunately, the vaccines that are currently available on the market do not meet these critical requirements. Therefore, we will have to wait for the right vaccine to arrive to combat Covid-19.

@pradipsinterpretations